效因子对氧气结合在R-四分制结构中的血红蛋白晶体的影响
1Division of Biophysics, Department of Physiology, Jichi Medical University, Shimotsuke, Tochigi, Japan.
Protein science : a publication of the Protein Society
|December 11, 2024
概括
贝扎菲布拉特及其衍生物L35在血红蛋白晶体的R状态下降低氧的亲和力. 这些效应剂降低了氧结合亲和力,而不会改变血红蛋白在放松 (R) 状态下的非合作氧化.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 生理学 生理学 生理学
背景情况:
- 效因子调节血红蛋白 (Hb) 的R和T状态,但它们对每个状态的内在O2亲和力的影响,特别是R状态,尚未完全理解.
- 在效应器结合的R状态Hb晶体中描述O2平衡对于理解全调节至关重要.
研究的目的:
- 为了彻底描述与效应器结合的和未结合的R-四边形晶体的O2平衡,马Hb.
- 确定诸如贝萨纤维酸盐 (BZF) 和伊诺西六酸盐 (IHP) 等效应剂如何影响Hb的R状态的O2亲和力.
主要方法:
- 结晶学以获得马Hb.的R-四元体晶体.
- 对效应器结合和未结合的晶体进行氧气平衡测量.
- 与BZF,L35和IHP进行联合结晶和浸泡实验.
主要成果:
- 马的Hb R状态晶体表现出高亲和度的非合作O2结合,类似于人类的Hb R状态晶体.
- 贝扎纤维酸 (BZF) 和其衍生品L35分别降低R状态Hb晶体的O2亲和力约3倍和2倍,保持非合作性结合.
- 这些亲和力减少是因效应诱导而产生的,而不是晶体包装的工件,并表明对T状态有轻微的四级转移.
结论:
- BZF衍生品通过诱导有利于向T状态转移的结构约束来降低R状态Hb O2亲和力.
- 伊诺西六酸盐 (IHP) 对R状态Hb O2亲和力和这种晶体形式的粘合力极少,这表明它可能无法有效地与R状态结构结合.
相关概念视频
Cooperative Allosteric Transitions
7.9K
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
7.9K
Allosteric Regulation
57.6K
Allosteric regulation of enzymes occurs when the binding of an effector molecule to a site that is different from the active site causes a change in the enzymatic activity. This alternate site is called an allosteric site, and an enzyme can contain more than one of these sites. Allosteric regulation can either be positive or negative, resulting in an increase or decrease in enzyme activity. Most enzymes that display allosteric regulation are metabolic enzymes involved in the degradation or...
57.6K
Oxygen Transport in the Blood
2.5K
Hemoglobin (Hb) is a crucial molecule in the human body, consisting of four polypeptide chains, each bound to an iron-containing heme group. This unique structure enables hemoglobin to bind to oxygen, with each molecule capable of combining with four molecules of oxygen, leading to rapid and reversible oxygen loading. When fully loaded with oxygen, it is called oxyhemoglobin, while hemoglobin that has released oxygen is called reduced hemoglobin or deoxyhemoglobin. As hemoglobin binds oxygen,...
2.5K
Protein and Protein Structure
78.5K
Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
A protein's shape is critical to its function. For example, an enzyme...
A protein's shape is critical to its function. For example, an enzyme...
78.5K
Allosteric Proteins-ATCase
5.7K
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
5.7K
Gene Families
8.8K
Gene families consist of groups of genes proposed to have originated from a common ancestor. Typically these arise through events in which a gene or genes are mistakenly duplicated during cell division. Unlike their parent genes (which are subject to selection pressure to maintain function), these gene copies do not need to preserve their sequences and may evolve at a relatively faster rate.
Occasionally these regions can be adapted to take on new roles within the organism, becoming novel genes...
Occasionally these regions can be adapted to take on new roles within the organism, becoming novel genes...
8.8K


